In relapsing EAE we have shown that a single clinical relapse and extensive CNS demyelination can be induced in animals sensitized with myelin/CFA and with MBP plus myelin lipids/CFA. The results suggest a role of myelin lipids in the pathogenesis of CNS demyelination in relapsing autoimmune disease. However, myelin proteins other than MBP and non-myelin proteins may be also involved in the pathogenesis of this model. From our studies it is also apparent that continuous presence of neuroantigen(s) is required for the establishment of chronic inflammation and/or extensive CNS demyelination. Work in progress is aimed at assessing the role of antibodies against myelin lipids and against MBP in the pathogenesis of CNS myelin destruction. In addition, the conditions required to induce continuous stimulation of the immune system in animals sensitized with neuroantigen(s) and the possibility that other myelin and non-myelin proteins may be also pathogenetically involved are being investigated.